Organ Enclosures For Inhibiting Tumor Invasion And Detecting Organ Pathology

ABSTRACT

An enclosure provides a prophylactic barrier that may be permeable to gases, hormones, proteins, and peritoneal fluid, but restrains tumor cells within the enclosure so as to inhibit ovarian cancer invasion of adjacent tissue, and increase the speed of diagnosis of ovarian dysplasia, including cancer. The enclosure includes one or more of fiducial markers, heat sensors, and blood flow reflectors, which may be imaged non-invasively in order to detect conditions or pathology affecting the ovary. The enclosure may also include an access port that permits sampling of the enclosure&#39;s contents to further aid in detecting or treating conditions or pathology affecting the ovary.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. provisional application Ser.No. 62/309,637 filed Mar. 17, 2016, which is incorporated herein byreference in its entirety.

FIELD

The disclosure relates to implantable devices for enclosing an organ,such as an ovary, in order to inhibit tumor cells, such as ovarian tumorcells, from invading adjacent tissue. The implantable enclosures areuseful, for example, for preserving one or both ovaries during ahysterectomy procedure, and for inhibiting invasive metastasis ofovarian tumors.

BACKGROUND

Various publications, including patents, published applications,technical articles and scholarly articles are cited throughout thespecification. Each of these cited publications is incorporated byreference herein, in its entirety and for all purposes.

There are over 100 recognized human cancer types, of which three maincategories effect the ovary: Epithelial Tumors (surface)=90% ofmalignant ovarian tumors; Germ Cell Tumors=5% of malignancies; andMetastatic Tumors (Krukenberg tumors originating elsewhere in body)=5%of malignancies. What is constant in these presentations is that eachcauses a cascade of events which may be observed. In the pre-cancerousstage, the ovary displays dysplasia, changes in surface topography andcharacteristics (e.g., lesions that may present as unusually hard orsoft areas of tissue, discolorations unrelated to ovulation, etc.). Toaid oncogenesis (progression to full blown cancer) increased bloodsupply is demanded from the organ, increasing its metabolism toaccommodate the demand for new vasculature formation (angiogenesis) andan inevitable inflammation of surrounding tissue in response to tumorformation.

The most consistent symptoms of ovarian cancer are morphologic (e.g.,dysplasia); it distorts the ovary's shape and swells the ovary, often tomany times its base-line size. This growth is often unaccompanied bydiscomfort or pain, as the ovary is designed to expand painlessly to aidprocreation (ovulation is normally accompanied by ovarian expansion).

Ovarian cancer persists undetected because the organ itself is difficultto image. Even methods employing extreme ionizing radiation, such as CTand PET scans do not accurately indicate ovarian tissue, even in themetastatic stages of ovarian cancer. Physicians do not employ suchdangerous imaging modalities for a routine annual pelvic exam but doemploy ultrasound sonography, itself a far less effective tool fordetecting ovarian tissue than is CT or PET scanning.

Pain is the overwhelming complaint driving the initial clinicalpresentation of women with ovarian cancer. One problem is that paincaused by ovarian cancer is usually the result of abdominal distensions,ascites, bloating, cramping and intestinal blockage; all signs ofmature, metastatic ovarian cancer at stage 3 or 4 development. Maturemetastatic ovarian cancer is the typical stage at diagnosis of ovariancancer and the result is dramatically poorer 5 year survival outcomesthan does early stage 1 or pre-cancerous diagnosis.

Hysterectomy procedures are quite common, with about 650,000 suchprocedures performed yearly in the United States alone. The procedure,which involves surgical removal of all or a portion of the uterus, isgenerally elective. Hysterectomy procedures are indicated due to pelviccancers in only 9% of all U.S. history (Hx).

As a form of defensive medicine (i.e., medical practices performedmainly to reduce the legal liability of the medical professionals)arising from a perceived risk of ovarian cancer, an elective bilateraloophorectomy (EBO) is commonly performed concomitant with thehysterectomy procedure. The EBO involves the removal of both ovaries. Anelective bilateral salpingo-oophprectomy (EBSO) includes fallopian tuberemoval in addition to the uterus, during the hysterectomy.

The most recent industry study determined EBO is performed in 69% ofopen hysterectomies, 60% of laparoscopic hysterectomies, and 30% ofvaginal hysterectomies for a total of 62% of all hysterectomies. It isestimated that EBO results in two to four times as many deaths asovarian cancer itself, taking into account the association betweenoophorectomy and decreased overall health and life expectancy, includingcontributing to the development of heart disease, a diminished cognitivecapacity, and osteoporosis. In fact, the American Medical Association(AMA) and the American Congress of Obstetricians and Gynecologists(ACOG) have conducted educational programs detailing patient harm due todefensive medical practices and labeled EBO a “practice of concern” totheir membership. Nevertheless, the removal of otherwise healthy ovariesduring hysterectomy procedures persists, as the perceived risk ofovarian cancer appears to outweigh the actual risks that materializefollowing EBO.

For its part, ovarian cancer is estimated to cause about 15,500 deathsper year, with mean age of detection around age 65 and death around age72. Ovarian cancer grows rapidly and metastasizes relatively early.Screening methods for ovarian cancer are somewhat deficient, at least asconcerns early detection.

Ovarian cancers typically do not disseminate/metastasize via the bloodor lymph. Rather, the ovarian cancer usually initially spreads viadirect invasion of adjacent tissue. Accordingly, it may be possible insome instances to contain ovarian cancer to the ovary, thereby reducingthe downstream pathologic risks, and advance indications such as painthat accelerate clinical presentation. This, in turn, should reduce theneed for defensive ovary removal.

SUMMARY

The present disclosure provides enclosures comprising: a biotextile, amedical textile, or both a biotextile and a medical textile; asuspensory ligament sleeve, an ovarian ligament sleeve, or both asuspensory ligament sleeve and an ovarian ligament sleeve; and aplurality of fiducial markers; wherein the enclosure has an elasticitythat allows the enclosure to expand in size; and wherein the biotextile,medical textile, or both the biotextile and the medical textile inhibitthe passage of live cells out from the enclosure.

The present disclosure also provides methods for inhibiting ovariantumor cell invasion of tissue adjacent to the ovary, comprisingenclosing one or both ovaries in a subject in need thereof with theenclosure according to any one of the embodiments disclosed herein,thereby inhibiting ovarian tumor cell invasion of tissue adjacent to oneor both ovaries in the subject.

The present disclosure also provides methods for treating a pathologiccondition of the ovary, comprising detecting a change in the location,position, or spacing of the plurality of fiducial markers of theenclosure according to any one of the embodiments disclosed herein whichhas been implanted in the body of a subject, obtaining a sample of theinternal contents of the enclosure, and determining the type ofpathologic condition of the ovary based on testing conducted on thesample, and treating the pathologic condition.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure can be understood from the following detaileddescription when read in connection with the accompanying drawings. Itis emphasized that, according to common practice, the various featuresof the drawing are not to scale. On the contrary, the dimensions of thevarious features are arbitrarily expanded or reduced for clarity.Included in the drawing are the following figures.

FIG. 1 shows an example of an ovarian enclosure, which comprises one ormore sleeves for enclosing at least a portion of one or more of thesuspensory ligament, the ovarian ligament, or blood vessels supplyingthe ovary.

FIG. 2 shows an example of an open and closed configuration of ligamentand blood vessel sleeves of the ovarian enclosure.

FIG. 3A shows an example of a clamp for securing a sleeve of the ovarianenclosure to a ligament or a blood vessel.

FIG. 3B shows an example of a plurality of clamps used to secure thesleeve to ligaments and blood vessels.

FIG. 4A shows an example of an ovarian enclosure having a plurality offiducial markers.

FIG. 4B shows an example of an ovarian enclosure having a plurality ofheat sensing markers.

FIG. 4C shows an example of an ovarian enclosure having a blood flowreflector.

FIG. 5A shows an example of an ovarian enclosure with an access port.

FIG. 5B shows an example of an ovarian enclosure with an access port anda seal or sealant.

FIG. 5C shows an example of an ovarian enclosure with an access port anda magnet or magnetic material.

FIG. 6 shows an example of an ovarian enclosure with an access port anda tube that is operably connected to the ovarian enclosure on theproximal side of the tube and to the access port on the distal side ofthe tube.

DETAILED DESCRIPTION

Various terms relating to embodiments of the disclosure are usedthroughout the specification and claims. Such terms are to be giventheir ordinary meaning in the art, unless otherwise indicated. Otherspecifically defined terms are to be construed in a manner consistentwith the definition provided herein.

As used herein, the singular forms “a,” “an,” and “the” include pluralreferents unless expressly stated otherwise.

The terms “subject” or “patient” are used interchangeably and refer toany animal. Mammals are suitable, and include companion and farmmammals, as well as rodents, including mice, rabbits, and rats, andother rodents. Primates are suitable, and human beings are exemplary.

The organ enclosures described herein are adapted and configured to atleast partially or completely encircle an organ of a mammal such thatorgan cells remain adjacent to the organ or within one or more layers ofthe enclosure. As a result, produced organ cells remain adjacent to theorgan or within the enclosure, thereby mitigating the admission ofproduced organ cells into the surrounding anatomical space. In someembodiments, an organ enclosure may include one or more anchoring orfixation elements to secure the enclosure to one or more of a layer ofan organ, a ligament of an organ, an artery or vein associated with anorgan or other structure associated with an organ.

The present disclosure provides organ enclosures that comprise abiotextile, a medical textile, or both a biotextile and a medicaltextile. The enclosure inhibits the passage of live organ cells (e.g.,cancer cells) out from the enclosure and has an elasticity that allowsthe enclosure to expand in size. The enclosure may further inhibitsurgical adhesions. The enclosure comprises one or more ligamentsleeves, and an optional port for accessing the internal contents of theenclosure. The enclosure may further comprise one or more blood vesselsleeves. The enclosure may further comprise a plurality of fiducialmarkers, which may be imaged or visualized by one or more of ultrasonicimaging, magnetic resonance imaging, or radiographic imaging, such asx-ray or tomography. The enclosure may comprise a single layer or aplurality of layers. The enclosure may comprise an outer layer and aninner layer, and a space between the outer layer and the inner layercapable of trapping live organ cells.

The organ enclosures described herein can be designed for any organ. Insome embodiments, the organ enclosure is an ovarian enclosure. In someembodiments, the organ enclosure is a kidney enclosure, a pancreasenclosure, a lobes of the lung enclosure, a liver enclosure, a spleenenclosure, a prostate gland enclosure, a stomach enclosure, an appendixenclosure, a gall bladder enclosure, a urinary bladder enclosure, or atesticle enclosure.

Referring now to the drawings, in which like reference numbers refer tolike elements throughout the various figures that comprise the drawings,FIG. 1 shows a perspective view of a first embodiment of an organenclosure. Although the drawings refer to an ovarian enclosure 10, thedrawings equally apply to any organ enclosure. The ovarian enclosure 10is biocompatible, and comprises a biotextile or medical textile suitablefor long-term, semi-permanent, or permanent implantation within thebody. Such biotextiles and medical textiles may comprise a natural orsynthetic material, or a combination of natural and synthetic materials.The ovarian enclosure 10 may serve a prophylactic role once implanted.

Biotextiles include materials obtained or derived from living tissue,including the stroma and extracellular matrix. Biotextiles may beobtained or derived from any source tissue including, but not limitedto, skin, pericardium, peritoneum, small or large intestine, stomach,and other suitable tissues. Biotextiles may comprise one or more ofautograft tissue, allograft tissue, or xenograft tissue. In someembodiments, the biotextile may comprise xenograft extracellular matrix.For xenograft tissue, the animal source may be a pig, cow, sheep, ornon-human primate. For allograft tissue, suitable live donors orcadavers may be used as the source. Biotextiles can be non-immunogenic,and can be devoid of growth factors and other factors that promotecellular invasion and vascularization, since the ovarian enclosure 10 isnot intended to function in the same capacity as a tissue repairscaffold.

Medical textiles include biocompatible synthetic materials. Examples ofsynthetic materials include, but are not limited to, polypropylene,polyethylene, polyvinyl chloride, polyurethane, polyethyleneterephthalate, poly-L-lactide, poly-DL-lactide, polyglycolic acid,poly(lactic-co-glycolic acid), polydioxanone, polytetrafluoroethylene,nylon, and copolymers thereof, and silicone rubbers or neoprene rubbers,metals and foils, as well as natural polymers such as collagen, gelatin,elastin keratin, actin, and polysaccharides such as cellulose, alginate,fibrin, amylose, chitin, dextran, and glycosaminoglycan. Any combinationof one or more of such materials may be used. In some embodiments, themedical textile comprises polypropylene. In some embodiments, themedical textile comprises polytetrafluoroethylene. In some embodiments,the medical textile comprises a silicone rubber. In some embodiments,the medical textile comprises a neoprene rubber. The enclosure may alsocomprise any combination of polypropylene, polytetrafluoroethylene,silicone rubber, or neoprene rubber.

In some embodiments, biotextiles and medical textiles may also be usedin combination. The biotextile or the medical textile may also comprisea biocompatible film.

In some embodiments, the enclosure 10 comprises a bioresorbable material(e.g., biotextile or medical textile) in combination with anon-resorbable material (e.g., biotextile or medical textile), which mayhelp to inhibit the formation of adhesions from the surgical procedure.Such a material may be resorbed by the body after a period of time,though the non-resorbable material remains, keeping the integrity andfunctionality of the enclosure 10 intact.

The biomedical and/or medical textiles may comprise any suitable form,including a mesh, weave, non-woven, sponge, foam, fabric, sheet, orfilm. The ovarian enclosure 10 may comprise one or more layers ofbiotextiles, medical textiles, or both biotextiles and medical textiles.In some embodiments, the ovarian enclosure 10 comprises a single layer.In some embodiments, the ovarian enclosure 10 comprises two layers,which may include a space in between. Each layer may comprise anysuitable thickness.

The layers of the ovarian enclosure 10 can be impermeable or porous,albeit selectively permeable. In some embodiments, the pore sizes are noless than about 100 picometers. In some embodiments, the pore sizes areno greater than about 1.0 micron. In some embodiments, the pore sizesare from about 100 picometers to about 1.0 micron, from about 100picometers to about 0.1 micron, or from about 100 picometers to about0.01 micron. Thus, biologic fluids (e.g., blood and abdominal fluid),hormones (e.g., follicle-stimulating hormone (FSH)), gases (e.g., oxygenand carbon dioxide), and waste materials (including cellular debris) mayfreely pass through the layers of the ovarian enclosure 10, such thatthe ovary may be properly perfused. However, live, intact ovary cells,including ovum, are prevented from passing through the layers of theovarian enclosure 10. In some embodiments of a multiple layeredenclosure 10, ovary cells or ovum may pass through the inner layer thatis adjacent to the ovary itself, but may not pass through the outerlayer of the enclosure 10—for example, such cells remain trapped in alumen 11 or space 11 located between the inner and outer layers. Thus,ovarian tumor cells are prevented from passing through the ovarianenclosure 10 once the enclosure 10 is properly implanted within thebody.

The ovarian enclosure 10 may be in the form of a capsule, bag, pouch,cloche, sack, wrap, envelope, or other suitable container. The ovarianenclosure 10 may be rigid or flexible, and may also be pliable orelastic, sufficient to expand to a point in the event that ovariancancer cells accumulate within the enclosure 10. In some embodiments,the ovarian enclosure 10 is flexible. In some embodiments, the ovarianenclosure 10 may have any suitable size, or length, width, and heightdimensions. In some embodiments, the ovarian enclosure 10 is tailored toa patient's particular ovary size.

In some embodiments, the ovarian enclosure 10 sufficiently flexes ormoves to accommodate patient movement and load forces, such that theenclosure 10, once implanted, does not cause pain from the patientbending or torqueing. In some embodiments, the ovarian enclosure 10 doesnot induce pain from intercourse. In some embodiments, the ovarianenclosure 10 has sufficient tensile strength such that it does not tearor break from patient movement or related stress.

In some embodiments, however, the ovarian enclosure 10 may be designedto be limited in its flexibility, such that it does not infinitelystretch in order to prevent pain felt by the subject. In cancerousstates, although an ovary may be enlarged, it is often not painful tothe subject. In such embodiments where the ovarian enclosure 10 isdesigned to be limited in its flexibility, pain may be perceived by thesubject having an enlarged, and possibly cancerous, ovary. Thus, anovarian enclosure that is designed to be limited in its flexibility mayaid in the diagnosis of a disease state whereby the subject perceivespain in the presence of the ovarian enclosure who may not otherwiseperceive the pain in the absence of the ovarian enclosure. In someembodiments, the ovarian enclosure may expand up to 75%, up to 80%, upto 85%, up to 90%, up to 95%, up to 100% (which would be a doubling inits expansion), up to 105%, up to 110%, up to 115%, up to 120%, up to125%, or up to 130%, thus allowing for expansion while still providingsufficient restriction to allow the subject to perceive pain.

In pliable or elastic embodiments, the material of the ovarian enclosure10 may expand about an additional 50% in size, though this expansiondoes not expand the pore size/porosity sufficiently to allow ovary cellsto pass though. The ovarian enclosure 10 may expand from about 1% toabout 50% in size, from about 1% to about 35%, from about 1% to about25%, from about 1% to about 20%, from about 1% to about 15%, from about1% to about 10%, from about 1% to about 5%, from about 5% to about 50%,from about 5% to about 25%, from about 5% to about 20%, from about 5% toabout 15%, from about 5% to about 10%, from about 10% to about 50%, fromabout 10% to about 40%, from about 10% to about 30%, from about 10% toabout 20%, from about 10% to about 15% in size, from about 20% to about50%, from about 20% to about 40%, from about 20% to about 35%, fromabout 25% to about 50%, from about 25% to about 40%, from about 30% toabout 50%, or from about 30% to about 40% in size. In some embodiments,the enclosure may expand up to about 50% in size. In some embodiments,the enclosure may expand up to about 33% in size. In some embodiments,the enclosure may expand up to about 25% in size. In some embodiments,the enclosure may expand up to about 10% in size. In some embodiments,the enclosure may expand more than 50% in size. In some embodiments, theenclosure may expand up to 55% in size, up to 55% in size, up to 60% insize, up to 65% in size, up to 70% in size, up to 75% in size, up to 80%in size, up to 85% in size, up to 90% in size, up to 95% in size, up to100% in size, up to 105% in size, up to 110% in size, up to 115% insize, up to 120% in size, up to 125% in size, up to 130% in size, up to135% in size, up to 140% in size, up to 145% in size, up to 150% insize, up to 155% in size, up to 160% in size, up to 165% in size, up to170% in size, up to 175% in size, up to 180% in size, up to 185% insize, up to 190% in size, up to 195% in size, or up to 200% in size.

In some embodiments, the organ enclosure has non-adherent propertiessuch that once implanted, the enclosure does not adhere to adjacenttissue. In some embodiments, the ovarian enclosure 10 also does notpromote cellular invasion or vascularization, and does not promotefibrosis or desmoplasia. In some embodiments, though biocompatible, theovarian enclosure 10 is biologically inert. In some embodiments, themeans of affixing the organ enclosure does not impede or interfere withthe organ vasculature. In some embodiments, the means of affixing theovarian enclosure does not impede or interfere with the ovarianvasculature.

Prior to a hysterectomy or other surgical alteration of the femalereproductive system, the ovary is ordinarily supported in place by asuspensory ligament, which attaches the ovary to the pelvic sidewall, anovarian ligament, which attaches the ovary to the uterus, and a broadligament, which supports the ovary (via the mesovarium) and itsvasculature. In a typical ovary-sparing hysterectomy procedure, theovarian ligament connection is severed, and the broad ligamentconnection is modified. The suspensory ligament, however remains.

Accordingly, in some embodiments, the ovarian enclosure 10 includes asuspensory ligament sleeve 14, and may further include an ovarianligament sleeve 16, and may further include one or more vasculaturesleeves 18 (see, FIG. 1). The suspensory ligament sleeve 14, the ovarianligament sleeve 16, and the one or more vasculature sleeves 18 extendfrom the main body of the enclosure 10, and enclose at least a portionof each ligament or blood vessels (arteries and veins) that supply theovary. The suspensory ligament sleeve 14 and the ovarian ligament sleeve16 may have any length suitable to ensure that cancerous ovary cellsthat cannot invade via a ligament. The one or more vasculature sleeves18 may also have any suitable length.

As the suspensory ligament, ovarian ligament (if retained), and bloodvessels remain attached to the body opposite their connection to theovary, the suspensory ligament sleeve 14, the ovarian ligament sleeve16, and the one or more vasculature sleeves 18 may, in some embodiments,be open before and during the initial stages of the procedure to implantthe ovarian enclosure 10, but then closed around their respectiveligament or blood vessels later during the implantation procedure (see,FIG. 2). To close the suspensory ligament sleeve 14, the ovarianligament sleeve 16, and the one or more vasculature sleeves 18, eachsleeve 14, 16, 18 may be sewn/sutured, glued, tied, banded, stapled,heat-sealed/melt-sealed, clamped, or otherwise sealed around theirrespective ligament or blood vessels.

In some embodiments, for example, where the ovarian ligament issurgically cut from the ovary, the ovarian enclosure 10 may include onlya suspensory ligament sleeve 14, and be otherwise sealed all the wayaround. In this manner, the enclosure is placed around the ovary, withone or more blood vessels and the suspensory ligament placed into andthrough the suspensory ligament sleeve 14, upon which the sleeve 14 maybe sewn/sutured, glued, tied, banded, stapled, heat-sealed/melt-sealed,clamped, or otherwise sealed around the suspensory ligament and bloodvessels.

In some embodiments, the suspensory ligament sleeve 14, the ovarianligament sleeve 16, and the one or more vasculature sleeves 18 aresealed around their respective ligament or blood vessels with a clamp20, for example, as shown in FIG. 3A. The clamp 20 may comprise a hinge22, as well as to ends 24 a and 24 b that surround an opening. Thus, theclamp 20 may be placed over top of the suspensory ligament sleeve 14,the ovarian ligament sleeve 16, or the one or more vasculature sleeves18, then closed by squeezing about the hinge, with the ends 24 a and 24b mating/locking/latching together. The ends 24 a and 24 b may comprisea ratchet or teeth and a pawl/lever, which allow the clamp 20 to closeto accommodate larger or smaller ligaments or blood vessels. A pluralityof clamps 20 may be used in conjunction with securing the ovarianenclosure 10 to the ovary (see, FIG. 3B).

Thus, in some embodiments, the enclosure further comprises one or moreclamps. For example, the enclosure may further comprise a first clampfor securing the suspensory ligament sleeve to the suspensory ligamentconnected to the ovary. The enclosure may further comprise one or moresecond clamps for securing the one or more blood vessel sleeves to bloodvessels connected to the ovary. The enclosure may further comprise afirst clamp for securing the suspensory ligament sleeve to thesuspensory ligament connected to the ovary and a third clamp forsecuring the ovarian ligament sleeve to the ovarian ligament connectedto the ovary. The enclosure may further comprise one or more secondclamps for securing the one or more blood vessel sleeves to bloodvessels connected to the ovary. Any of the first clamp, second clamp, orthird clamp may comprise a hinge, a first end, and a second end, and thefirst end and second end are capable of locking together. In someembodiments, the attachment can be carried out without using claims. Forexample, a biocompatible glue, which may be approved for internal use,may be used. In some embodiments, a suture or barb, or other means, suchas friction or a deformation made permanent (such as a foil), or aprocess that cures after attachment, such as a silicon gel, may be used.

Thus, the ovarian enclosure 10 is implanted and is attached to at leastthe suspensory ligament, as well as blood vessels and, in some cases, tothe ovarian ligament. In some embodiments, the enclosure 10 envelopes,but is not affixed to the ovary itself. In some embodiments, however,the enclosure 10 is affixed directly to one or more surfaces of theovary, for example, via an adhesive, or via a form of shrink-wrapping orkinetic distortion, e.g., a foil-like wrap. In some embodiments, noportion of the ovarian enclosure adheres to the surface of the ovary. Insome embodiments, a portion of the ovarian enclosure adheres to thesurface of the ovary.

The ovarian enclosure 10 is surgically implanted, and is suitable forimplantation via an open/laparotomy type procedure, or via alaparoscopic procedure. The ovarian enclosure 10, and its sleeves 14,16, 18 may be applied to their respective anatomical structure viaunrolling, wrapping, spraying, extrusion, or insertion of the structureinto the enclosure 10. An ovarian enclosure 10 may be implanted over theright ovary or the left ovary; separate enclosures 10 are used whereboth the right and left ovaries are enclosed. In some embodiments, itmay be suitable to retain and enclose at least the left ovary in orderto avoid confusion with appendicitis associated with right-side painpresentation.

The ovarian enclosure 10 may comprise additional features to aid in thedetection of pathologic conditions affecting the ovaries, includingovarian cysts and ovarian cancer. As the enclosure 10 has a finitecapacity to expand, abnormal growth of the ovary will assert pressureagainst the enclosure 10, causing localized pain in the area. The painmay, in turn, allow the patient to seek treatment of the conditionearlier than she ordinarily might have sought treatment, especially if,absent the presence of the enclosure, the condition would remainasymptomatic, at least for some additional period of time. Thepathological conditions aided by these additional features include, forexample, dysplasia, pain, motility of the surface(hardening—oophosclerosis; softening—oophomalacia), and physicalcharacteristics such as, for example, relative temperature, increasedblood flow, and lesion identification.

To facilitate detection of an ovarian pathology, the enclosure 10 maycomprise a plurality of fiducial markers 30 (see, FIG. 4A) that may bevisualized via standard imaging techniques such as x-rays, ultrasound,magnetic resonance imaging, or tomography. If the enclosure 10 expands,the distance between fiducial markers 30 will expand, indicating to thepractitioner that there may be a pathologic condition occurring with theovary in the enclosure 10. Relatedly, the regionalization of expandedfiducial markers 30 may indicate the location of the pathology. Thepathology may include one or more of inflammation, cysts, neoplasm,hyperplasia, hyperthecosis, or other ovarian growth or tumor, whetherbenign or malignant.

To facilitate detection of an ovarian pathology, the enclosure 10 maycomprise a plurality of heat sensing markers 40 (see, FIG. 4B), whichmay be visualized via standard imaging techniques such as x-rays,ultrasound, magnetic resonance imaging, or tomography. The heat sensingmarkers 40 may, for example, comprise a thermal shape memory materialsuch as nitinol, which would cause the markers 40 to expand or enlargein the event of elevated heat, with the presence of heat indicating apathology. In some embodiments, the heat sensing marker can be athermister, a fiber optic, or graphene.

To facilitate detection of an ovarian pathology, the enclosure 10 maycomprise one or more blood flow reflectors 50 (see, FIG. 4C), which maybe used in connection with a flow meter that measures volume or velocityof blood flow into and/or out from the blood vessels that supply theovary. Detection of blood volume or flow velocity may be used to detectthe presence of an ovarian pathology.

In some embodiments, the enclosure 10 may comprise a port 60, whichallows access to the internal contents of the enclosure 10 (see FIG. 5A;top drawing is a perspective view; bottom drawing is a partialcross-section view), or the trap lumen 11 between the inner and outerlayers of the enclosure 10. Access via the port 60 avoids the need tocompromise the enclosure 10.

The port may further comprise a valve that closes the port but iscapable of being opened when a probe presses the valve inward. The portmay further comprise a seal or a sealant. The seal or sealant maycomprise one or more of a biocompatible polymer, biocompatible gel,biocompatible wax, or biocompatible rubber such as a biocompatiblesilicone rubber. The port may further comprise one or more fiducialmarkers, one or more magnets, and/or one or more magnetic metals. Theport may be operably connected to a tube that is also operably connectedto the ovarian enclosure.

The port 60 may comprise a valve 62 that closes the port 60 when accessis not desired. To gain access, an external probe such as a needle,tube, or catheter is inserted through the valve 62, from which ovariantissue or other contents of the enclosure 10 may be aspirated orotherwise sampled/removed. In addition or in the alternate, the probemay be used to administer a therapeutic agent to treat a condition ofthe ovary (e.g., any ovarian condition described or exemplified herein)through the valve 62 port 60. Thus, the port 60 also allows forlocalized treatment of the ovary. The probe may, in some embodiments,insufflate the enclosure 10 via the valve 62, for example, to clear anydebris that may block the probe or otherwise impede the probe's accessor capacity to sample within the enclosure 10.

In the alternate, or in addition to the valve 62, the port may furthercomprise a seal or sealant 64 through which the probe may be inserted(see, FIG. 5B; top drawings is a perspective view; the bottom drawing isa partial cross-section view). The seal or sealant 64 prevents escape ofthe enclosure 10 contents, including cancerous cells, in the event ofvalve 62 failure or by the puncture action of the probe (the seal orsealant 64 immediately closes around and off the probe while the probeis inserted, and the sealant recloses once the probe is removed). Theseal or sealant 64 may comprise any suitable material, such as abiocompatible plastic, polymer, rubber, gel, wax, or silicone material.

Therapeutic agents to treat any condition of the ovary may beadministered locally to the ovary through the sealant 64 and via theport 60. The probe may, in some embodiments, insufflate the enclosure 10via the seal or sealant 64, for example, to clear any debris that mayblock the probe or otherwise impede the probe's access or capacity tosample within the enclosure 10. In some embodiments, the neck of theenclosure can be loosened to allow insertion of a biodegradeablechemotherapeutic eluting polymer construct. In some embodiments, thewalls of the enclosure could be pierced or cut to allow insertion of anagent and patched following insertion.

Therapeutic agents that can be administered locally to the ovary mayinclude biomolecules or chemical molecules, or combinations thereof.Categories of such agents include, but are not limited to,chemotherapeutic agents, anti-inflammatory agents, pain-relievingagents, and other agents suitable for the ovarian condition beingtreated. Suitable chemotherapeutic agents include, but are not limitedto, Paclitaxel (Taxor), albumin bound paclitaxel (nab-paclitaxel,Abraxane®), Altretamine (Hexalen®), Capecitabine (Xeloda®),Cyclophosphamide (Cytoxan®, Clafen®, Neosar®), Etoposide (VP-16),Gemcitabine (Gemzar®), Ifosfamide (Ifex®), Irinotecan (CPT-11,Camptosar®), Liposomal doxorubicin (Doxil®, Dox-SL®, Evacet®, LipoDox®)Alkeran (Melphalan), Pemetrexed (Alimta®), Topotecan (Hycamtin®),Vinorelbine (Navelbine®), Bevacizumab (Avastin®), Carboplatin, Cisplatin(Platinol®, Platinol-AQ®), Olaparib (Lynparza®), Carboplatin (Paraplat®,Paraplatin®), Rucaparib Camsylate (Rubraca®), and Thiotepa. In someembodiments, the chemotherapeutic agent is a combination of a platinumcompound, such as cisplatin or carboplatin, and a taxane, such aspaclitaxel (Taxol®) or docetaxel (Taxotere®). Other combinationsinclude, but are not limited to, a combination of bleomycin, etoposide,cisplatin (BEP), Carboplatin-Taxol, Gemcitabine-Cisplatin, a combinationof carboplatin (JM8), etoposide phosphate, and bleomycin sulfate (JEB),a combination of vincristine sulfate, dactinomycin (actinomycin-D), andcyclophosphamide (VAC), and a combination of vinblastine, ifosfamide andcisplatin (VeIP). One advantage of treating an ovary with a therapeuticagent using the ovarian enclosure is that the therapeutic agent remainsin close proximity to the ovary, and conversely, surrounding tissue ismore apt to be protected from contact with the therapeutic agent. Forexample, the ovarian enclosure may affect therapeutic delivery ofchemotherapeutic agents, such as Cisplatin, by keeping them in closeproximity to the ovarian surface epithelium whilst protecting thoseagents from dissemination and dilution, and equally protecting proximaltissues from exposure to agents that may be harmful to those surroundingtissues.

In addition, the ovarian enclosure may be used to affix variousdiagnostic tools in close proximity to the epithelial surface of theovary. For example, diagnostic biomarkers, such as HE4-9, EIA, andUrokinase Plasminogen Activator (u-PA) may have superior sensitivity andspecificity to CA-125. Additional biomarkers include, but are notlimited to: protein/antigen (e.g., CA-125, HE4, SMRP, OPN, VEGF, TTR,ApoA1, B7-H4, KLKs, PRSS8, M-CSF, LPA, IL-8, IL-6, OVX1, VCAM1, AGR-2,MMP-7, Serum Amyloid A), gene, DNA hypo/hyper-methylation (e.g.,hypermethylated: BRCA1, p16, MLH1, RASSF1A, OPCML, LOT1, DAPK, PAR-4,ICAM-1, SPARC; hypomethylated: MCJ, SNCG, TRAG-3, IGF2, Claudin-4),histone modification (e.g., up-regulated: HDAC1-3, Rb, CDKN1;down-regulated: Class III b-tubulin, survivin, PACE4, Claudin-3, GATA4,GATA6), micro-RNA (e.g., up-regulated: miR-200a, miR-141, miR-200c,miR-200b, miR-203, miR-205; down-regulated: miR-199a, mIR-140, miR-145,miR-125b1, let-7i), and metabolites. These biomarkers may benefit fromassured proximity and exclusive exposure to the ovarian surface.

The port 60 may be accessed surgically, for example, via a smallincision. In some embodiments, the port 60 is accessed minimallyinvasively, for example, by inserting the probe directly through theskin and into the port 60. To this end, the fiducial markers 30 mayindicate the location of the port 60 and, thus, assist in guiding theprobe toward and into the port 60.

In addition or in the alternate to the fiducial markers 30, the port 60may comprise a magnet 66 or magnetic metal 68 (see, FIG. 5C; the topdrawing is a perspective view; the bottom drawing is a partialcross-section view). In such embodiments, the probe may include thecognate magnetic structure, such as a magnet when the port 60 comprisesa magnetic metal 68, or such as a magnetic metal when the port 60comprises a magnet 66. In this manner, the interaction of the magnet(66) and magnetic metal (68) on the port 60 and probe assist in guidingthe probe toward and into the port 60.

In some embodiments, the port 60 may further be connected to a tube 70.For example, the tube 70 may be connected directly to the ovarianenclosure 10, with the port 60 located distally from the ovarianenclosure 10 (see, FIG. 6). This may permit less invasive access to thecontents of the enclosure 10. For example, the tube 70 may extend intothe vaginal canal, thus permitting the probe to be inserted into thevagina and into the port 60 within the vaginal canal, rather thanpuncturing the skin with the probe or with an incision to allow probeinsertion into the body. Vaginal access also offers the additionaladvantage of avoiding the need for guided insertion as the port 60should be visible to the practitioner. The tube 70 may be surgicallyfastened to the vaginal canal, for example, to avoid impedingintercourse or to avoid discomfort or to avoid feeling movement of thetube 70. For example, the tube may be fastened to a vaginal cuffestablished during the hysterectomy procedure. Alternately, the port 60may be implanted at the body surface, for example, the navel, with thetube 70 extending through the body to the enclosure 10. In someembodiments, a body surface port 60 may also be covered by dermis toprevent external contamination.

In embodiments where the port 60 is located at a distal end of the tube70 (opposite the end of the tube 70 connected to the enclosure 10), theport 60 may similarly comprise one or more of a valve 62, seal orsealant 64, magnet 66, or magnetic metal 68, as described above, toensure that the integrity of the enclosure 10 is maintained, as well asto assist in accessing the port 60, even if the port 60 can otherwise bevisualized without the need for imaging equipment.

The disclosure also provides methods for inhibiting the invasion oftissue adjacent to the organ by tumor cells. In some embodiments, themethods inhibit the invasion of tissue adjacent to the ovary by ovariantumor cells. In general, the methods comprise implanting any embodimentof the organ enclosure, such as the ovarian enclosure 10 described orexemplified herein, into the body of the subject in need thereof. Forexample, the ovarian enclosure 10 is implanted by enclosing the ovarywithin the ovarian enclosure 10. In addition to the ovary, one or moreof the suspensory ligament, the ovarian ligament, and the blood vessels(veins and/or arteries) that supply the ovary may be enclosed within theovarian enclosure 10, for example, via the suspensory ligament sleeve14, the ovarian ligament sleeve 16, and the one or more vasculaturesleeves 18, which are sealed around their respective ligament or bloodvessels.

The methods for inhibiting ovarian tumor cell invasion of tissueadjacent to the ovary generally comprises enclosing one or both ovariesin a subject in need thereof with any of the ovarian enclosures,including any features, described or exemplified herein. Enclosing oneor both ovaries inhibits ovarian tumor cell invasion of tissue adjacentto one or both ovaries in the subject. Inhibiting ovarian tumor cellinvasion may thus inhibit ovarian cancer metastasis. Where the enclosurecomprises a suspensory ligament sleeve, the method may further compriseanchoring the suspensory ligament sleeve to the suspensory ligamentconnected to the ovary. Where the enclosure comprises an ovarianligament sleeve, the method may further comprise anchoring the ovarianligament sleeve to the ovarian ligament connected to the ovary. Wherethe enclosure comprises one or more blood vessel sleeves, the method mayfurther comprise anchoring the one or more blood vessel sleeves to oneor more blood vessels connected to the ovary. Such anchoring steps maybe performed according to any technique suitable or desired by themedical practitioner, and may comprise one or more of gluing, suturing,clamping, or otherwise fastening the sleeve to the ligament or bloodvessel, as the case may be.

The ovarian enclosures described herein may contain cancer progressionif the ovary is already growing neoplasms at the time of hysterectomy.The ovarian enclosures described herein may deflect micro-migrationsfrom the fallopian tubes.

An ovary may be enclosed, for example, during a hysterectomy procedureor other form of abdominal surgery. It is not necessary to enclose anovary with the ovarian enclosure 10 as secondary to another surgery, asthe enclosure 10 may be used in a stand-alone procedure, for example, inthe event that the subject is determined to be at a heightened risk todevelop ovarian cancer. In any case, either the left, right, or bothovaries may be enclosed.

The disclosure also provides methods for detecting a pathologiccondition of an organ. In some embodiments, the methods providedetection of a pathologic condition of an ovary. In some embodiments,the methods comprise imaging one or more of the fiducial markers 30, theheat sensing markers 40, or the blood flow reflector 50 on an ovarianenclosure 10 implanted in the body of a subject. The imaging of the oneor more of the fiducial markers 30, the heat sensing markers 40, or theblood flow reflector 50 may be according to any suitable imagingmodality. A change in the location, spacing, or position of the fiducialmarkers 30 or the heat sensing markers 40 indicates an enlargement orbulge, or contraction at a particular portion of the ovarian enclosure10 or of the ovarian enclosure 10 on the whole, thus indicating a changein the normal or healthy condition of the ovary. The pathologiccondition may be benign or malignant. The pathologic condition mayinclude ovarian atrophy, inflammation, cysts, neoplasm, hyperplasia,hyperthecosis, or other ovarian growth or tumor, whether the tumor isbenign or malignant. The methods may further comprise treating thepathologic condition.

In some embodiments, a biomarker or other suitable marker that may beused to indicate a condition of the ovary may be incorporated orsuspended within the enclosure 10. Such a marker may by detectable orsampled from the enclosure 10, for example, via the port 60. Such amarker may react with, for example, a cancerous condition to aid in thedetection of such a condition.

In some embodiments, the methods comprise, or further comprise, samplingthe internal contents of the ovarian enclosure. Sampling the contentsmay comprise inserting a probe, such as a needle or catheter, throughthe sidewalls of the ovarian enclosure 10, essentially compromising theenclosure. Alternately, sampling the contents may comprise inserting aprobe, such as a needle or catheter, into the port 60 of the ovarianenclosure 60, which does not compromise the enclosure. The sampledcontents may then be subject to further testing to determine the natureof the sampled contents, including whether or not the contents indicatethat there is a change in the normal or healthy condition of the ovary,including the presence of a pathologic condition. The methods mayfurther comprise treating the pathologic condition.

In some embodiments, a method for treating a pathologic condition of theovary comprises detecting a change in the location, position, or spacingof the plurality of fiducial markers of the ovarian enclosure, and/orobtaining a sample of the internal contents of the ovarian enclosure,and then determining the type of pathologic condition of the ovary basedon testing conducted on the sample, and then treating the pathologiccondition. Obtaining a sample or the internal contents and/or treatingthe pathologic condition may comprise inserting a probe into the ovarianenclosure, for example, via a port in the enclosure. The probe may thenbe used to aspirate a sample of the enclosure contents, and/oradminister a therapeutic agent locally to the ovary. If the condition isovarian cancer, treating the cancer may comprise removing the cancerousovary from the subject, or may comprise administering chemotherapeuticagents to the ovary, for example, via a port in the enclosure. If thecondition is an ovarian cyst, treating the cyst may comprise removingthe cyst or the ovary from the subject, or may comprise administering acyst-treating therapeutic agent to the ovary, for example, via a port inthe enclosure.

The ovarian enclosures described herein provide numerous advantages.First, the ovarian enclosures described herein will assist techniciansin defining the ovarian surface through routine sonographic tools,deployed topically or intra-vaginally. By conforming to ovarian tissueand being compliant to its morphoses, the enclosures will providefiducial markers to accurately convey any deviation from baseline sizeor shape of the ovary.

Although the ovary expands virtually painlessly, it is similar to themale testicle in its sensitivity to compression. In addition, althoughthe ovarian implant will conform to and be compliant to the surface ofthe ovary, at some point its expansion will generate enough compressionof ovarian tissue to cause pain. When the pain is great enough, thewoman will seek clinical intervention. The implant will act as aconstant and passive diagnostic tool to accelerate clinical presentationwith pain, and increase the incidence of the clinical diagnosis of,early stage 1 ovarian cancer.

As a tumor matures within the ovary, it demands vastly greater resourcesthan does healthy ovarian tissue. Accordingly, this change in metabolismmay be detected through the relative temperature of the ovary incomparison to adjacent tissue. Once a base-line ratio is established,any deviation unrelated to ovulation may demand further inquiry. Bloodflow is a corollary indication of unusual ovarian activity. Sensors maybe placed to generate perfusion data to further assist doctors in makingan accurate diagnosis.

Another advantage of using an organ enclosure is the possible avoidanceof unnecessarily removing the organ itself.

The following representative embodiments are presented:

Embodiment 1

An enclosure comprising:

-   -   a biotextile, a medical textile, or both a biotextile and a        medical textile;    -   a suspensory ligament sleeve, an ovarian ligament sleeve, or        both a suspensory ligament sleeve and an ovarian ligament        sleeve;    -   a plurality of fiducial markers; and    -   an optional port for accessing the internal contents of the        enclosure;    -   wherein the enclosure has an elasticity that allows the        enclosure to expand in size; and    -   wherein the biotextile, medical textile, or both the biotextile        and the medical textile inhibit the passage of live ovarian        cells out from the enclosure.

Embodiment 2

The enclosure according to embodiment 1, wherein the biotextilecomprises xenograft extracellular matrix.

Embodiment 3

The enclosure according to embodiment 1 or 2, wherein the medicaltextile comprises polypropylene, polyethylene, polyvinyl chloride,polyurethane, polyethylene terephthalate, poly-L-lactide,poly-DL-lactide, polyglycolic acid, poly(lactic-co-glycolic acid),polydioxanone, polytetrafluoroethylene, or nylon, or any copolymerthereof.

Embodiment 4

The enclosure according to any one of embodiments 1 to 3, wherein themedical textile comprises polypropylene.

Embodiment 5

The enclosure according to any one of embodiments 1 to 3, wherein themedical textile comprises polytetrafluoroethylene.

Embodiment 6

The enclosure according to embodiment 1 or 2, wherein the medicaltextile comprises a silicone rubber.

Embodiment 7

The enclosure according to embodiment 1 or 2, wherein the medicaltextile comprises a neoprene rubber.

Embodiment 8

The enclosure according to any one of embodiments 1 to 7, wherein thebiotextile or the medical textile comprises a biocompatible film.

Embodiment 9

The enclosure according to any one of embodiments 1 to 8, wherein theenclosure comprises a plurality of layers.

Embodiment 10

The enclosure according to embodiment 9, wherein the enclosure comprisesan outer layer and an inner layer, and a space between the outer layerand the inner layer capable of trapping live ovarian cells.

Embodiment 11

The enclosure according to any one of embodiments 1 to 10, wherein thebiotextile or the medical textile have an elasticity that allows theenclosure to expand up to about 50% in size.

Embodiment 12

The enclosure according to any one of embodiments 1 to 11, wherein thebiotextile or the medical textile have an elasticity that allows theenclosure to expand up to about 33% in size.

Embodiment 13

The enclosure according to any one of embodiments 1 to 12, wherein thebiotextile or the medical textile have an elasticity that allows theenclosure to expand up to about 25% in size.

Embodiment 14

The enclosure according to any one of embodiments 1 to 13, wherein thebiotextile or the medical textile have an elasticity that allows theenclosure to expand up to about 10% in size.

Embodiment 15

The enclosure according to any one of embodiments 1 to 14, wherein theenclosure comprises a suspensory ligament sleeve, but not an ovarianligament sleeve.

Embodiment 16

The enclosure according to any one of embodiments 1 to 15, furthercomprising one or more blood vessel sleeves.

Embodiment 17

The enclosure according to any one of embodiments 1 to 16, furthercomprising a first clamp for securing the suspensory ligament sleeve tothe suspensory ligament connected to the ovary.

Embodiment 18

The enclosure according to any one of embodiments 1 to 17, furthercomprising one or more second clamps for securing the one or more bloodvessel sleeves to blood vessels connected to the ovary.

Embodiment 19

The enclosure according to any one of embodiments 1 to 14, furthercomprising a first clamp for securing the suspensory ligament sleeve tothe suspensory ligament connected to the ovary, and a third clamp forsecuring the ovarian ligament sleeve to the ovarian ligament connectedto the ovary.

Embodiment 20

The enclosure according to embodiment 19, further comprising one or moresecond clamps for securing the one or more blood vessel sleeves to bloodvessels connected to the ovary.

Embodiment 21

The enclosure according to any one of embodiments 17 to 20, wherein thefirst clamp comprises a hinge, a first end, and a second end, and thefirst end and second end are capable of locking together.

Embodiment 22

The enclosure according to embodiment 18 or 20, wherein the one or moresecond clamps comprise a hinge, a first end, and a second end, and thefirst end and second end are capable of locking together.

Embodiment 23

The enclosure according to embodiment 19 or 20, wherein the third clampcomprises a hinge, a first end, and a second end, and the first end andsecond end are capable of locking together.

Embodiment 24

The enclosure according to any one of embodiments 1 to 23, furthercomprising one or more heat sensing markers.

Embodiment 25

The enclosure according to any one of embodiments 1 to 24, furthercomprising a blood flow reflector.

Embodiment 26

The enclosure according to any one of embodiments 1 to 25, wherein theport further comprises a valve that closes the port but is capable ofbeing opened when a probe presses the valve inward.

Embodiment 27

The enclosure according to any one of embodiments 1 to 26, wherein theport further comprises a seal or a sealant.

Embodiment 28

The enclosure according to embodiment 27, wherein the seal or sealantcomprises a biocompatible polymer.

Embodiment 29

The enclosure according to embodiment 27, wherein the seal or sealantcomprises a biocompatible gel.

Embodiment 30

The enclosure according to embodiment 27, wherein the seal or sealantcomprises a biocompatible wax.

Embodiment 31

The enclosure according to embodiment 27, wherein the seal or sealantcomprises a biocompatible rubber.

Embodiment 32

The enclosure according to embodiment 31, wherein the biocompatiblerubber comprises silicone.

Embodiment 33

The enclosure according to any one of embodiments 1 to 32, wherein theenclosure further comprises one or more fiducial markers.

Embodiment 34

The enclosure according to any one of embodiments 1 to 33, wherein theport further comprises a magnet.

Embodiment 35

The enclosure according to any one of embodiments 1 to 33, wherein theport further comprises a magnetic metal.

Embodiment 36

The enclosure according to any one of embodiments 1 to 35, wherein theport is operably connected to a tube that is also operably connected tothe ovarian enclosure.

Embodiment 37

The enclosure according to any one of embodiments 1 to 36, wherein thefiducial markers are capable of being visualized by ultrasonic imaging.

Embodiment 38

The enclosure according to any one of embodiments 1 to 37, wherein thefiducial markers are capable of being visualized by magnetic resonanceimaging.

Embodiment 39

The enclosure according to any one of embodiments 1 to 38, wherein thefiducial markers are capable of being visualized by radiographicimaging.

Embodiment 40

The enclosure according to embodiment 39, wherein the radiographicimaging comprises tomography.

Embodiment 41

The enclosure according to any one of embodiments 1 to 40, wherein thebiotextile is anti-adhesive, non-immunogenic, and does not promotecellular invasion or vascularization of the biotextile.

Embodiment 42

The enclosure according to any one of embodiments 1 to 41, wherein themedical textile is anti-adhesive.

Embodiment 43

The enclosure according to any one of embodiments 1 to 42, whereinovarian cells comprise ovarian cancer cells.

Embodiment 44

A method for inhibiting ovarian tumor cell invasion of tissue adjacentto the ovary, comprising enclosing one or both ovaries in a subject inneed thereof with the enclosure according to any one of embodiments 1 to43, thereby inhibiting ovarian tumor cell invasion of tissue adjacent toone or both ovaries in the subject.

Embodiment 45

The method according to embodiment 44, wherein the method furthercomprises anchoring the suspensory ligament sleeve to the suspensoryligament connected to the ovary by suturing the suspensory ligamentsleeve to said suspensory ligament.

Embodiment 46

The method according to embodiment 44, wherein the method furthercomprises anchoring the suspensory ligament sleeve to the suspensoryligament connected to the ovary by gluing the suspensory ligament sleeveto said suspensory ligament.

Embodiment 47

The method according to embodiment 44, wherein the method furthercomprises anchoring the ovarian ligament sleeve to the ovarian ligamentconnected to the ovary by suturing the ovarian ligament sleeve to saidovarian ligament.

Embodiment 48

The method according to embodiment 44, wherein the method furthercomprises anchoring the ovarian ligament sleeve to the ovarian ligamentconnected to the ovary by gluing the ovarian ligament sleeve to saidovarian ligament.

Embodiment 49

The method according to embodiment 44, wherein the method furthercomprises anchoring the one or more blood vessel sleeves to one or moreblood vessels connected to the ovary by suturing the one or more bloodvessels sleeves to said one or more blood vessels.

Embodiment 50

The method according to embodiment 44, wherein the method furthercomprises anchoring the one or more blood vessel sleeves to one or moreblood vessels connected to the ovary by gluing the one or more bloodvessels sleeves to said one or more blood vessels.

Embodiment 51

The method according to any one of embodiments 44 to 50, wherein thesubject is a human being.

Embodiment 52

A method for treating a pathologic condition of the ovary, comprisingdetecting a change in the location, position, or spacing of theplurality of fiducial markers of the enclosure according to any one ofembodiments 1 to 43 which has been implanted in the body of a subject,obtaining a sample of the internal contents of the enclosure anddetermining the type of pathologic condition of the ovary based ontesting conducted on the sample, and treating the pathologic condition.

Embodiment 53

The method according to embodiment 52, wherein obtaining a samplecomprises inserting a probe into the enclosure and aspirating thesample.

Embodiment 54

The method according to embodiment 53, wherein the probe is insertedinto the port.

Embodiment 55

The method according to any one of embodiments 52 to 54, where treatingthe pathologic condition comprises administering a therapeutic agentlocally to the ovary via a port in the enclosure.

Embodiment 56

The method according to any one of embodiments 52 to 54 wherein thepathologic condition is ovarian cancer and treating the pathologiccondition comprises removing one or both of ovaries from the subject.

Embodiment 57

The method according to any one of embodiments 52 to 54, wherein thepathologic condition is ovarian cysts and treating the pathologiccondition comprises removing the ovarian cysts from one or both ofovaries of the subject.

In order that the subject matter disclosed herein may be moreefficiently understood, examples are provided below. It should beunderstood that these examples are for illustrative purposes only andare not to be construed as limiting the claimed subject matter in anymanner.

EXAMPLES Example 1 Partial Enclosure—Ophidian Spiral Thread of Silicon

In one embodiment, the ovarian enclosure is an ophidian spiral thread ofsilicon that may enhance the clinician's efforts to image the ovariansurface. This structure may be held in place by friction, glue or asimple fastening method such as a suture placed at one or more locationsto avoid future motility of the ovarian enclosure.

Example 2 Complete Enclosure

A complete containment of the ovarian surface can be accomplished with avery thin silicon enclosure, applied much like unrolling a condom.Silicon may add to the opacity of the ovary to aid ovarian surfaceimaging, but should elements such as metallic particulates need to beadded to the silicon to enhance its opacity, it must adhere to andconform to the surface of the ovary. This structure may be held in placeby friction, glue or a simple fastening method such as a suture placedat one or more locations to avoid future motility of the ovarianenclosure.

Example 3 Multiple Layered Ovarian Enclosure

In another embodiment, the ovarian enclosure involves multiple layers ofmaterials, each designed to perform a specific task. The outer layer mayserve the purpose of an anti-adhesive or anti-microbial layer to preventimmediate post-surgical complications. This outer layer may beconstructed of hyaluronic acid, Rifampin impregnated Tyrosine, or otheragents approved for internal use that may eventually break down throughhydrolysis.

The inner layer(s) may include a thin silicon layer to aid in imaging asdescribed above, and an inner layer or layers of material, such aspolyesters with varying weave porosity designed to impede ovarianexpansion beyond a certain multiple of base-line size, or containcellular migrations between various layers.

This enclosure may be wrapped around the ovary and set with variousbiocompatible glues such as Cohera Medical's TissuGlu.

The disclosure is not limited to the embodiments described andexemplified above, but is capable of variation and modification withinthe scope of the appended claims.

1. An enclosure comprising: a biotextile, a medical textile, or both abiotextile and a medical textile; a suspensory ligament sleeve, anovarian ligament sleeve, or both a suspensory ligament sleeve and anovarian ligament sleeve; and a plurality of fiducial markers; whereinthe enclosure has an elasticity that allows the enclosure to expand insize; and wherein the biotextile, medical textile, or both thebiotextile and the medical textile inhibit the passage of live ovariancells out from the enclosure.
 2. The enclosure according to claim 1,wherein the biotextile comprises xenograft extracellular matrix.
 3. Theenclosure according to claim 1, wherein the medical textile comprisespolypropylene, polyethylene, polyvinyl chloride, polyurethane,polyethylene terephthalate, poly-L-lactide, poly-DL-lactide,polyglycolic acid, poly(lactic-co-glycolic acid), polydioxanone,polytetrafluoroethylene, or nylon, or any copolymer thereof.
 4. Theenclosure according to claim 1, wherein the medical textile comprises asilicone rubber or a neoprene rubber.
 5. The enclosure according toclaim 1, wherein the biotextile or the medical textile comprises abiocompatible film.
 6. The enclosure according to claim 1, wherein theenclosure comprises a plurality of layers.
 7. The enclosure according toclaim 1, wherein the biotextile or the medical textile have anelasticity that allows the enclosure to expand up to about 10%, up toabout 25%, up to about 33%, or up to about 50% in size.
 8. The enclosureaccording to claim 1, further comprising one or more blood vesselsleeves.
 9. The enclosure according to claim 1, further comprising: aclamp for securing the suspensory ligament sleeve to the suspensoryligament connected to the ovary; and/or a clamp for securing the ovarianligament sleeve to the ovarian ligament connected to the ovary. 10.(canceled)
 11. The enclosure according to claim 8, further comprisingone or more clamps for securing the one or more blood vessel sleeves toblood vessels connected to the ovary.
 12. The enclosure according toclaim 9, wherein each clamp comprises a hinge, a first end, and a secondend, and the first end and second end are capable of locking together.13. The enclosure according to claim 1, further comprising one or moreheat sensing markers and/or a blood flow reflector.
 14. (canceled) 15.The enclosure according to claim 1, wherein the fiducial markers arecapable of being visualized by ultrasonic imaging, magnetic resonanceimaging, or radiographic imaging.
 16. The enclosure according to claim1, wherein the biotextile is anti-adhesive, non-immunogenic, and doesnot promote cellular invasion or vascularization of the biotextile. 17.The enclosure according to claim 1, wherein the medical textile isanti-adhesive.
 18. A method for inhibiting ovarian tumor cell invasionof tissue adjacent to the ovary, comprising enclosing one or bothovaries in a subject in need thereof with the enclosure according toclaim 1, thereby inhibiting ovarian tumor cell invasion of tissueadjacent to one or both ovaries in the subject.
 19. The method accordingto claim 18, wherein the method further comprises: anchoring thesuspensory ligament sleeve to the suspensory ligament connected to theovary by suturing the suspensory ligament sleeve to said suspensoryligament or by gluing the suspensory ligament sleeve to said suspensoryligament; and/or anchoring the ovarian ligament sleeve to the ovarianligament connected to the ovary by suturing the ovarian ligament sleeveto said ovarian ligament or by gluing the ovarian ligament sleeve tosaid ovarian ligament; and/or anchoring the one or more blood vesselsleeves to one or more blood vessels connected to the ovary by suturingthe one or more blood vessels sleeves to said one or more blood vesselsor by gluing the one or more blood vessels sleeves to said one or moreblood vessels. 20-22. (canceled)
 23. A method for treating a pathologiccondition of the ovary, comprising detecting a change in the location,position, or spacing of the plurality of fiducial markers of theenclosure according to claim 1 which has been implanted in the body of asubject, obtaining a sample of the internal contents of the enclosure,and determining the type of pathologic condition of the ovary based ontesting conducted on the sample, and treating the pathologic condition.24. The method according to claim 23, wherein treating the pathologiccondition comprises administering a therapeutic agent locally to theovary.
 25. The method according to claim 23, wherein the pathologiccondition is ovarian cancer, and treating the pathologic conditioncomprises removing one or both of ovaries from the subject or thepathologic condition is ovarian cysts, and treating the pathologiccondition comprises removing the ovarian cysts from one or both ofovaries of the subject.